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Erschienen in: Current Treatment Options in Gastroenterology 4/2018

13.09.2018 | Pancreas (V Chandrasekhara, Section Editor)

Pancreatic Cancer and Diabetes Mellitus

verfasst von: Ayush Sharma, MBBS, Suresh T. Chari, MD

Erschienen in: Current Treatment Options in Gastroenterology | Ausgabe 4/2018

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Abstract

Purpose of review

The relationship between pancreatic ductal adenocarcinoma (PDAC) and diabetes mellitus (DM) is complex. We reviewed the recent medical literature regarding the effect of anti-diabetic medication on PDAC risk and survival, risk of PDAC in DM, and role of DM in early detection of PDAC.

Recent findings

Studies report that while some anti-diabetic medications (e.g., metformin) may decrease the risk of PDAC, others (insulin, sulfonylureas and incretin-based therapies) may increase the risk. However, these observations may be subject to protopathic biases. Metformin’s anti-tumor activity may have influence overall survival of PDAC, but epidemiological reports have largely been inconsistent to defend these findings due to heterogeneous methodologies. There is congruent data to support the association between DM and PDAC, with an inverse relationship to DM duration. Older subjects with new-onset DM are the only known high-risk group for PDAC, and strategy using this group for early detection has led to development of clinical risk prediction models that define a very high-risk PDAC group.

Summary

Role of anti-diabetic medication in PDAC risk modification or survival is controversial. With successful efforts to distinguish type 2-DM from PDAC-DM using risk-stratifying models, there is an opportunity to initiate screening protocols for early detection of PDAC in a sub-set of DM subjects.
Literatur
1.
Zurück zum Zitat Sah RP, Nagpal SJS, Mukhopadhyay D, Chari ST. New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastroenterol Hepatol. 2013;10(7):423–33.CrossRefPubMedPubMedCentral Sah RP, Nagpal SJS, Mukhopadhyay D, Chari ST. New insights into pancreatic cancer-induced paraneoplastic diabetes. Nat Rev Gastroenterol Hepatol. 2013;10(7):423–33.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat • Andersen DK, Korc M, Petersen GM, Eibl G, Li D, Rickels MR, et al. Diabetes, pancreatogenic diabetes, and pancreatic cancer. Diabetes. 2017;66(5):1103–10. https://doi.org/10.2337/db16-1477. This reports highlights key research gaps in relationship between PDAC and DM as identified by experts at a symposium held at the American Diabetic Association 76th scientific session.CrossRefPubMedPubMedCentral • Andersen DK, Korc M, Petersen GM, Eibl G, Li D, Rickels MR, et al. Diabetes, pancreatogenic diabetes, and pancreatic cancer. Diabetes. 2017;66(5):1103–10. https://​doi.​org/​10.​2337/​db16-1477. This reports highlights key research gaps in relationship between PDAC and DM as identified by experts at a symposium held at the American Diabetic Association 76th scientific session.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat • Chen H, Zhou X, Chen T, Liu B, Jin W, Gu H, et al. Incretin-based therapy and risk of pancreatic Cancer in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Diabetes Ther. 2016;7(4):725–42. https://doi.org/10.1007/s13300-016-0198-3. The only meta-analysis including all randomized control trials of incretin-based therapy showing no short-term increased risk of PDAC in DM patients on incretin-based therapy.CrossRefPubMedPubMedCentral • Chen H, Zhou X, Chen T, Liu B, Jin W, Gu H, et al. Incretin-based therapy and risk of pancreatic Cancer in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Diabetes Ther. 2016;7(4):725–42. https://​doi.​org/​10.​1007/​s13300-016-0198-3. The only meta-analysis including all randomized control trials of incretin-based therapy showing no short-term increased risk of PDAC in DM patients on incretin-based therapy.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Hong H, Yong F, Hongming P, et al. Relationship of metformin with the risk of pancreatic cancer in patients with type 2 diabetes: a meta-analysis. Biomedical Research (0970-938X) [serial online]. 2017;28(10):4439–4444. Available from: Academic Search Premier, Ipswich, MA. Accessed September 10, 2018. Hong H, Yong F, Hongming P, et al. Relationship of metformin with the risk of pancreatic cancer in patients with type 2 diabetes: a meta-analysis. Biomedical Research (0970-938X) [serial online]. 2017;28(10):4439–4444. Available from: Academic Search Premier, Ipswich, MA. Accessed September 10, 2018.
19.
Zurück zum Zitat Horwitz RI, Feinstein AR. The problem of “protopathic bias” in case-control studies. Am J Med. 1980;68(2):255–8.CrossRefPubMed Horwitz RI, Feinstein AR. The problem of “protopathic bias” in case-control studies. Am J Med. 1980;68(2):255–8.CrossRefPubMed
21.
Zurück zum Zitat Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD). Diabetes Care. 2012;35(6):1364–79. https://doi.org/10.2337/dc12-0413.CrossRefPubMedPubMedCentral Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD). Diabetes Care. 2012;35(6):1364–79. https://​doi.​org/​10.​2337/​dc12-0413.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat • Sharma A, Smyrk TC, Levy MJ, Topazian MA, Chari ST. Fasting blood glucose levels provide estimate of duration and progression of pancreatic cancer before diagnosis. Gastroenterology. 2018; https://doi.org/10.1053/j.gastro.2018.04.025. This is the first study that estiamted the pre-diagnostic duration of invasive PDAC using blood glucose as a bio-marker of early PDAC and show hyperglycemia in PDAC preceeds by 30 to 36 months prior to PDAC diagnosis and this hyperglycemia is associated with a certain tumor volume.CrossRefPubMed • Sharma A, Smyrk TC, Levy MJ, Topazian MA, Chari ST. Fasting blood glucose levels provide estimate of duration and progression of pancreatic cancer before diagnosis. Gastroenterology. 2018; https://​doi.​org/​10.​1053/​j.​gastro.​2018.​04.​025. This is the first study that estiamted the pre-diagnostic duration of invasive PDAC using blood glucose as a bio-marker of early PDAC and show hyperglycemia in PDAC preceeds by 30 to 36 months prior to PDAC diagnosis and this hyperglycemia is associated with a certain tumor volume.CrossRefPubMed
35.
Zurück zum Zitat •• Chaiteerakij R, Petersen GM, Bamlet WR, Chaffee KG, Zhen DB, Burch PA, et al. Metformin use and survival of patients with pancreatic Cancer: a cautionary lesson. J Clin Oncol. 2016;34(16):1898–904. https://doi.org/10.1200/JCO.2015.63.3511. This study highlights the importance of patient selection and appropriate statistical analysis methods used when studying medication exposure and cancer survival.CrossRefPubMedPubMedCentral •• Chaiteerakij R, Petersen GM, Bamlet WR, Chaffee KG, Zhen DB, Burch PA, et al. Metformin use and survival of patients with pancreatic Cancer: a cautionary lesson. J Clin Oncol. 2016;34(16):1898–904. https://​doi.​org/​10.​1200/​JCO.​2015.​63.​3511. This study highlights the importance of patient selection and appropriate statistical analysis methods used when studying medication exposure and cancer survival.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST. Prevalence and clinical profile of pancreatic cancer–associated diabetes mellitus. Gastroenterology. 2008;134(4):981–7.CrossRefPubMed Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST. Prevalence and clinical profile of pancreatic cancer–associated diabetes mellitus. Gastroenterology. 2008;134(4):981–7.CrossRefPubMed
39.
Zurück zum Zitat Chari ST, Leibson CL, Rabe KG, Ransom J, De Andrade M, Petersen GM. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology. 2005;129(2):504–11.CrossRefPubMed Chari ST, Leibson CL, Rabe KG, Ransom J, De Andrade M, Petersen GM. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology. 2005;129(2):504–11.CrossRefPubMed
40.
41.
Zurück zum Zitat •• Aggarwal G, Rabe KG, Petersen GM, Chari ST. New-onset diabetes in pancreatic cancer: a study in the primary care setting. Pancreatology. 2012;12(2):156–61. https://doi.org/10.1016/j.pan.2012.02.003. This is the first study highlighting the importance of delays in diagnosis of diabetes by physcian’s and its implications in early detection of PDAC.CrossRefPubMed •• Aggarwal G, Rabe KG, Petersen GM, Chari ST. New-onset diabetes in pancreatic cancer: a study in the primary care setting. Pancreatology. 2012;12(2):156–61. https://​doi.​org/​10.​1016/​j.​pan.​2012.​02.​003. This is the first study highlighting the importance of delays in diagnosis of diabetes by physcian’s and its implications in early detection of PDAC.CrossRefPubMed
43.
Zurück zum Zitat •• Boursi B, Finkelman B, Giantonio BJ, Haynes K, Rustgi AK, Rhim AD, et al. A clinical prediction model to assess risk for pancreatic cancer among patients with new-onset diabetes. Gastroenterology. 2017;152(4):840–50.e3. This clinical risk prediction model uses physcian diagnosis of new-onset diabetes and based on various demographic, clinical and biochemical parameters at the time of NOD diagnosis predict 3-year risk of PDAC.CrossRefPubMed •• Boursi B, Finkelman B, Giantonio BJ, Haynes K, Rustgi AK, Rhim AD, et al. A clinical prediction model to assess risk for pancreatic cancer among patients with new-onset diabetes. Gastroenterology. 2017;152(4):840–50.e3. This clinical risk prediction model uses physcian diagnosis of new-onset diabetes and based on various demographic, clinical and biochemical parameters at the time of NOD diagnosis predict 3-year risk of PDAC.CrossRefPubMed
45.
Zurück zum Zitat •• Sharma A, Kandlakunta H, Singh Nagpal SJ, Ziding F, Hoos W, Petersen GM, et al. Model to determine risk of pancreatic cancer in patients with new-onset diabetes. Gastroenterology. 2018; https://doi.org/10.1053/j.gastro.2018.05.023. This is the first clinical risk prediction model that uses glycemic definition of new-onset DM and identifies a very high risk group for PDAC (~4% 3-year risk) that may benefit from clinical work-up.CrossRefPubMed •• Sharma A, Kandlakunta H, Singh Nagpal SJ, Ziding F, Hoos W, Petersen GM, et al. Model to determine risk of pancreatic cancer in patients with new-onset diabetes. Gastroenterology. 2018; https://​doi.​org/​10.​1053/​j.​gastro.​2018.​05.​023. This is the first clinical risk prediction model that uses glycemic definition of new-onset DM and identifies a very high risk group for PDAC (~4% 3-year risk) that may benefit from clinical work-up.CrossRefPubMed
46.
Zurück zum Zitat Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis. Diabetes Care. 1992;15(7):815–9.CrossRefPubMed Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4-7 yr before clinical diagnosis. Diabetes Care. 1992;15(7):815–9.CrossRefPubMed
61.
Zurück zum Zitat Rex DK. Colonoscopy: a review of its yield for cancers and adenomas by indication. Am J Gastroenterol. 1995;90(3):353–65.PubMed Rex DK. Colonoscopy: a review of its yield for cancers and adenomas by indication. Am J Gastroenterol. 1995;90(3):353–65.PubMed
Metadaten
Titel
Pancreatic Cancer and Diabetes Mellitus
verfasst von
Ayush Sharma, MBBS
Suresh T. Chari, MD
Publikationsdatum
13.09.2018
Verlag
Springer US
Erschienen in
Current Treatment Options in Gastroenterology / Ausgabe 4/2018
Print ISSN: 1092-8472
Elektronische ISSN: 1534-309X
DOI
https://doi.org/10.1007/s11938-018-0197-8

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